| 1. |
- Andersson, Jonas, 1969-
(författare)
-
Adipose tissue as an active organ : blood flow regulation and tissue-specific glucocorticoid metabolism
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite advances in the treatment of atherosclerosis, cardiovascular disease is the leading cause of death worldwide. With the population getting older and more obese, the burden of cardiovascular disease may further increase. Premenopausal women are relatively protected against cardiovascular disease compared to men, but the reasons for this sex difference are partly unknown. Redistribution of body fat from peripheral to central depots may be a contributing factor. Central fat is associated with hyperlipidemia, hyperglycemia, hypertension, and insulin resistance. Two possible mediators of these metabolic disturbances are tissue-specific production of the stress hormone cortisol and adipose tissue blood flow (ATBF). The aim of this thesis was to determine the adipose tissue production of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and to investigate the regulation of ATBF. Materials and Methods: Cortisol release was estimated by labeled cortisol infusions and tissue-specific catheterizations of subcutaneous and visceral adipose tissue (VAT) in men. We investigated ATBF by 133Xe-washout and its relation to autonomic activity, endothelial function, adipose tissue distribution, and adipokines in different groups of women. We further investigated the effect of two diets and of weight loss on ATBF in women. Results: We demonstrated significant cortisol release from subcutaneous adipose tissue in humans. Splanchnic cortisol release was accounted for entirely by the liver. Cortisol release from VAT (to the portal vein) was not detected. ATBF decreased according to increasing weight and postmenopausal status, and the level of blood flow was associated with nitric oxide (NO) activity and autonomic activity. ATBF was also highly associated with leptin levels and both subcutaneous adipose tissue and VAT areas. After 6 months of diet and weight reduction, a significant difference in ATBF was observed between diet groups. Conclusions: Our data for the first time demonstrate the contributions of cortisol generated from subcutaneous adipose tissue, visceral tissues, and liver by 11β-HSD1. ATBF is linked to autonomic activity, NO activity, and the amount of adipose tissue (independent of fat depot). Postmenopausal overweight women exhibited a loss of ATBF flexibility, which may contribute to the metabolic dysfunction seen in this group. Weight loss in a diet program could not increase the ATBF, although there were ATBF differences between diet groups. The results will increase understanding of adipose tissue biology and contribute to the development of treatment strategies targeting obesity and obesity-related disorders.
|
|
| 2. |
- Andersson, Jonas, et al.
(författare)
-
Association of adipose tissue blood flow with fat depot sizes and adipokines in women
- 2012
-
Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 36:6, s. 783-789
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore possible associations between adipose tissue (AT) blood flow (ATBF), AT depot sizes and adipocyte-derived hormones (adipokines) in women.Subjects: In all, 43 healthy women were divided into four groups: normal-weight (n=11) and obese (n=11) pre-menopausal women and normal-weight (n=10) and obese (n=11) post-menopausal women.Methods: Fasting levels of adipokines were obtained, and a single-slice computed tomography scan at the level of L4-L5 was used to estimate fat depot sizes. ATBF was assessed by xenon washout while in a fasting state and after oral glucose load. We also measured glucose, insulin and non-esterified fatty acids.Results: Total, subcutaneous and visceral AT areas strongly correlated with ATBF (all P<0.001). Circulating leptin levels strongly and inversely correlated with ATBF (P=0.001), but this association did not remain after adjustment for body mass index. Adiponectin was not associated with blood flow.Conclusion: ATBF is closely linked to subcutaneous and visceral AT size. Further analyses are needed to determine possible mediators of this association, including mechanistic studies to assess a putative role for leptin as a significant modulator of blood flow. International Journal of Obesity advance online publication, 26 July 2011; doi:10.1038/ijo.2011.152.
|
|
| 3. |
- Andersson, Jonas, et al.
(författare)
-
Dysregulation of subcutaneous adipose tissue blood flow in overweight postmenopausal women
- 2010
-
Ingår i: Menopause. - : Ovid Technologies (Wolters Kluwer Health). - 1072-3714 .- 1530-0374. ; 17:2, s. 365-371
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A putative link between abdominal obesity and metabolic-vascular complications after menopause may be due to a decreased adipose tissue blood flow (ATBF). The present work aimed to analyze possible changes in ATBF with being overweight and menopausal and its putative link to endothelial dysfunction and autonomic nervous system balance.METHODS: Forty-three healthy women were classified into four groups according to weight and menopause status. The ATBF was measured by xenon washout while fasting and after oral glucose intake. The nitric oxide synthase inhibitor asymmetric dimethylarginine was used as a marker of endothelial function and heart rate variability-estimated autonomic nervous system activity.RESULTS: Fasting ATBF was decreased in both overweight groups (P = 0.044 and P = 0.048) versus normal-weight premenopausal women. Normal-weight and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight premenopausal women (P = 0.015 and P = 0.001, respectively), and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight postmenopausal women (P = 0.003). A negative correlation was found between fasting ATBF and asymmetric dimethylarginine (P = 0.015), whereas maximum ATBF was negatively associated with sympathetic-parasympathetic nervous system balance (ratio of the power of the low frequency to the power of the high frequency; P = 0.002).CONCLUSIONS: Loss of ATBF flexibility in overweight postmenopausal women may contribute to the metabolic dysfunction seen in this group of women.
|
|
| 4. |
- Andersson, Jonas, et al.
(författare)
-
Left ventricular remodelling changes without concomitant loss of myocardial fat after long-term dietary intervention
- 2016
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 216, s. 92-96
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulation of myocardial triglycerides (MTG) is associated with impaired left ventricular (LV) remodelling and function in obese and diabetic subjects. The role of MTG accumulation in development of heart failure in this group of patients is unknown. Short-term studies suggest that diets that lead to weight loss could mobilize MTG, with a favourable effect on cardiac remodelling. In a 24-month, randomized, investigator-blinded study, we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women. Methods: Sixty-eight healthy postmenopausal women with body mass index [BMI] >= 27 kg/m(2) were randomized to an ad libitum Palaeolithic diet (PD) or a Nordic Nutrition Recommendation (NNR) diet for 24 months. Morphology, cardiac function, and MTG levels were measured using magnetic resonance (MR) scanning, including proton spectroscopy at baseline and 6 and 24 months. Results: Despite mean weight losses of 4.9 (1.0) kg (NNR) and 7.8 (1.1) kg (PD), the MTG content did not change over time (p = 0.98 in the NNR and p = 0.11 in the PD group at 24 months). Reduced left ventricular mass was observed in both diet groups over 24 months. Blood pressure was reduced at 6 months, but returned to baseline levels at 24 months. End diastolic volume, stroke volume, and cardiac output decreased over time. No differences between diet groups were observed. Conclusions: Diet intervention and moderate weight loss over 24 months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
|
|
| 5. |
|
|
| 6. |
- Dahlman, Ingrid, et al.
(författare)
-
A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects
- 2005
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 90:10, s. 5834-5840
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. Objectives: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. Design: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human sc adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. Results: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. Conclusions: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.
|
|
| 7. |
- Lång, P, et al.
(författare)
-
Expression and secretion of the novel adipokine tartrate-resistant acid phosphatase from adipose tissues of obese and lean women
- 2011
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 35:12, s. 1502-1510
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Tartrate-resistant acid phosphatase (TRAP) expressed by adipose tissue macrophages (ATMs) induces mice obesity and human adipocyte differentiation in vitro. This study aimed to investigate whether TRAP was secreted differently from human obese versus lean adipose tissues and to identify the cellular source of adipose tissue TRAP.Design: Subcutaneous adipose tissues obtained from healthy subjects. Enzyme-linked immunosorbent assays (ELISAs) for total (5a+5b) and cleaved TRAP (5b) were used. TRAP secretion was determined in adipose tissue biopsies, and mRNA expression was studied in cell types isolated from the same.Subjects: Results of 24 lean and 24 obese women (in vitro) and 8 subjects (in vivo) were compared. The main outcome measurements were TRAP expression and secretion in vitro and in vivo.Results: In-house total TRAP ELISA showed high sensitivity and a coefficient of variance of 11%. Adipose secretion of total TRAP was linear in vitro with time and was evident in vivo. Total TRAP secretion in vitro was similar in lean and obese women expressed per unit weight of the adipose tissue but correlated positively with the number/size of adipocytes (P≤0.01) and with adipose secretion of tumor necrosis factor-α and interleukin-6 (P<0.01). TRAP 5b was not secreted from the adipose tissue. ATMs displayed highest cellular expression of TRAP mRNA in adipose tissue cells derived from lean or obese women.Conclusions: TRAP is a novel human adipokine produced by macrophages and secreted from the subcutaneous adipose tissue in vivo and in vitro. Secretion is linked to the size and number of adipocytes, as well as to concomitant secretion of inflammatory mediators, suggesting that TRAP is involved in fat accumulation and adipose inflammation. International Journal of Obesity advance online publication, 8 March 2011; doi:10.1038/ijo.2011.17.
|
|
| 8. |
- Mattsson, Cecilia, et al.
(författare)
-
Gender-specific links between hepatic 11beta reduction of cortisone and adipokines
- 2007
-
Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 15:4, s. 887-894
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones. RESEARCH METHODS AND PROCEDURES: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. RESULTS: Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. DISCUSSION: Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
|
|
| 9. |
- Otten, Julia, 1973-, et al.
(författare)
-
Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus
- 2019
-
Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell. - 2047-9980 .- 2047-9980. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function.Methods and Results: Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group.Conclusions: Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus.Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.
|
|
| 10. |
- Stimson, Roland H, et al.
(författare)
-
Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans
- 2009
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 58:1, s. 46-53
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11beta-HSD1 from adipose tissue and its effect on portal vein cortisol concentrations have not been quantified in vivo.RESEARCH DESIGN AND METHODS: Six healthy men underwent 9,11,12,12-[(2)H](4)-cortisol infusions with simultaneous sampling of arterialized and superficial epigastric vein blood sampling. Four men with stable chronic liver disease and a transjugular intrahepatic porto-systemic shunt in situ underwent tracer infusion with simultaneous sampling from the portal vein, hepatic vein, and an arterialized peripheral vein.RESULTS: Significant cortisol and 9,12,12-[(2)H](3)-cortisol release were observed from subcutaneous adipose tissue (15.0 [95% CI 0.4-29.5] and 8.7 [0.2-17.2] pmol . min(-1) . 100 g(-1) adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[(2)H](3)-cortisol (13.5 [3.6-23.5] and 8.0 [2.6-13.5] nmol/min, respectively) was accounted for entirely by the liver; release of cortisol from visceral tissues into portal vein was not detected.CONCLUSIONS: Cortisol is released from subcutaneous adipose tissue by 11beta-HSD1 in humans, and increased enzyme expression in obesity is likely to increase local glucocorticoid signaling and contribute to whole-body cortisol regeneration. However, visceral adipose 11beta-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.
|
|
